Focused Ultrasound Therapy
Focused ultrasound is a rapidly evolving, noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with liver tumors. This novel technology focuses beams of ultrasound energy precisely and accurately on targets deep in the body without damaging surrounding normal tissue.
How it Works
Where the beams converge, focused ultrasound produces several therapeutic effects that are being evaluated.
One mechanism is the production of precise ablation (thermal destruction of tissue). This destruction can be done to completely destroy the target or to partially treat it, and partial treatment is believed to stimulate the patient’s immune response, which may have a broader impact.
Another mechanism is the use of mechanical (non-thermal) histotripsy to destroy the tumor.
A third mechanism is to use focused ultrasound to cause hyperthermia which enables the local release and absorption of a therapeutic that is contained in the blood stream.
Advantages
The primary options for treatment of liver tumors include surgery, chemotherapy, radiotherapy, localized destruction of the tumor tissue (via radiofrequency ablation, alcohol injection, cryosurgery, or laser photocoagulation), or combination of two or more of these options. The long-term solution for primary liver cancer is often liver transplantation.
For certain patients, focused ultrasound could provide a noninvasive alternative to surgery with less risk of complications – such as surgical wound healing or infection – at a lower cost. It can reach the desired target without damaging surrounding tissue and is repeatable, if necessary. Focused ultrasound can also enhance the chemotherapy dose for the target, with less impact to the rest of the patient.
Clinical Trials
A clinical trial in the UK is recruiting patients with colorectal cancer and metastasis to the liver. It uses focused ultrasound to activate a microbubble preparation designed to improve the penetration of chemotherapy to the liver.
A clinical study involves enhancing drug delivery due to heating the thermosensitive lysosome containing chemotherapy with focused ultrasound in pediatric patients and young adults.
A clinical trial in Trondheim, Norway, is using focused ultrasound to pre-treat patients with metastatic lesions in their liver due to colorectal cancer before chemotherapy doses.
A clinical trial in Tours, France, is using focused ultrasound to enhance the penetration of therapeutic medications in patients who have liver metastatic lesions from colorectal cancer.
A clinical trial is recruiting patients with solid tumors with metastatic lesions, including liver cancer, at the University of Virginia.
A pair of clinical trials are using histotripsy to treat liver tumors. The trial in the US is close to completion and is targeting 45 participants. Treatment locations in the US are at Miami Cancer Institute ivettec@BaptistHealth.net , Tampa General Hospital abader@tgh.org , University of Chicago plofton@radiology.bsd.uchicago.edu, University of Kansas packerman@kumc.edu, University of Michigan Hospital vkh@med.umich.edu, University of Wisconsin UW South jyakey@uwhealth.org, and Medical College of Wisconsin/Froedtert Hospital badion@mcw.edu. The trial in Europe has completed enrollment with 24 participants.
For a full list of clinical trials, please click here.
See a list of treatment sites >
See a list of laboratory research sites >
Regulatory Approval and Reimbursement
A focused ultrasound system has been approved in China, Russia, Europe, and Korea for treatment of liver cancer.
To the best of our knowledge, the use of focused ultrasound to treat liver cancer is not yet widely reimbursed by medical insurance.
Notable Papers
Wang J, Wan L, Huang G, Chen C, Wu Y. Comparison of high-intensity focused ultrasound and microwave ablation for the treatment of small liver metastatic tumors. J Int Med Res. 2023 Apr;51(4):3000605231165551. doi: 10.1177/03000605231165551.
Zou YW, Ren ZG, Sun Y, Liu ZG, Hu XB, Wang HY, Yu ZJ. The latest research progress on minimally invasive treatments for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2023 Feb;22(1):54-63. doi: 10.1016/j.hbpd.2022.08.004. Epub 2022 Aug 19.
Wah TM, Pech M, Thormann M, Serres X, Littler P, Stenberg B, Lenton J, Smith J, Wiggermann P, Planert M, Vidal-Jove J, Torzilli G, Solbiati L. A Multi-centre, Single Arm, Non-randomized, Prospective European Trial to Evaluate the Safety and Efficacy of the HistoSonics System in the Treatment of Primary and Metastatic Liver Cancers (#HOPE4LIVER). Cardiovasc Intervent Radiol. 2023 Feb;46(2):259-267. doi: 10.1007/s00270-022-03309-6. Epub 2022 Nov 15.
Mauch SC, Zlevor AM, Knott EA, Couillard AB, Periyasamy S, Williams EC, Swietlik JF, Laeseke PF, Zhang X, Xu Z, Abel EJ, Lee FT Jr, Ziemlewicz TJ. Hepatic and Renal Histotripsy in an Anticoagulated Porcine Model. J Vasc Interv Radiol. 2023 Mar;34(3):386-394.e2. doi: 10.1016/j.jvir.2022.11.034. Epub 2022 Dec 9.
Xiao C, Liu S, Ge G, Jiang H, Wang L, Chen Q, Jin C, Mo J, Li J, Wang K, Zhang Q, Zhou J. Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies. Front Pharmacol. 2023 Feb 6;14:1086813. doi: 10.3389/fphar.2023.1086813. eCollection 2023.
Froghi S, de Andrade MO, Hadi LM, Gelat P, Rashidi H, Quaglia A, Fuller B, Saffari N, Davidson B. Liver Ultrasound Histotripsy: Novel Analysis of the Histotripsy Site Cell Constituents with Implications for Histotripsy Application in Cell Transplantation and Cancer Therapy. Bioengineering (Basel). 2023 Feb 20;10(2):276. doi: 10.3390/bioengineering10020276.
Robinson TP, Pebror T, Krosin ME, Koniaris LG. Ablative Therapy in Non-HCC Liver Malignancy. Cancers (Basel). 2023 Feb 14;15(4):1200. doi: 10.3390/cancers15041200.
Cambronero S, Dupré A, Mastier C, Melodelima D. Non-invasive High-Intensity Focused Ultrasound Treatment of Liver Tissues in an In Vivo Porcine Model: Fast, Large and Safe Ablations Using a Toroidal Transducer. Ultrasound Med Biol. 2023 Jan;49(1):212-224. doi: 10.1016/j.ultrasmedbio.2022.08.015. Epub 2022 Oct 28.
Elfatairy K. First-In-Human Histotripsy Trial for Liver Tumor Treatment: The New Echo Superpower. Radiol Imaging Cancer. 2023 Jan;5(1):e229026. doi: 10.1148/rycan.229026.
Tang X, He X, Jiang H. Efficacy and safety of HIFU in combination with TACE in unresectable pediatric HB: A randomized, controlled, single-center clinical trial. Medicine (Baltimore). 2022 Dec 2;101(48):e32022. doi: 10.1097/MD.0000000000032022.
Guntur SR, Kim SC, Choi MJ. A Cost-Effective Reusable Tissue Mimicking Phantom for High Intensity Focused Ultrasonic Liver Surgery. Bioengineering (Basel). 2022 Dec 9;9(12):786. doi: 10.3390/bioengineering9120786.
Zou X, Li T, Mao Y, Zhu M, Chen X, Niu J, Dong T, Jiang J, Yang X. Multifunctional Drug-Loaded Phase-Change Nanoparticles Inhibit the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Affecting the Activity of Activated Hepatic Stellate Cells. Biomed Res Int. 2022 Nov 12;2022:6441179. doi: 10.1155/2022/6441179. eCollection 2022.
Knott EA, Zlevor AM, Hinshaw JL, Laeseke PF, Longhurst C, Frank J, Bradley CW, Couillard AB, Rossebo AE, Xu Z, Lee FT Jr, Ziemlewicz TJ. A comparison study of microwave ablation vs. histotripsy for focal liver treatments in a swine model. Eur Radiol. 2022 Sep 1. doi: 10.1007/s00330-022-09112-8.
Shi S, Li H, Zheng X, Lv L, Liao S, Lu P, Liu M, Zhao H, Mei Z. Visualization system based on hierarchical targeting for diagnosis and treatment of hepatocellular carcinoma. Mater Today Bio. 2022 Aug 22;16:100398. doi: 10.1016/j.mtbio.2022.100398. eCollection 2022 Dec.
Heo J, Joung C, Pahk K, Pahk KJ. Investigation of the long-term healing response of the liver to boiling histotripsy treatment in vivo. Sci Rep. 2022 Aug 24;12(1):14462. doi: 10.1038/s41598-022-18544-7.
Zhang L, Qiao L, Zhang M, Xue Y, Zhang X, Gao X. Comparison of prognosis among patients with colorectal cancer liver metastases treated by surgical resection, radiofrequency ablation and HIFU: A protocol for network meta-analysis. Medicine (Baltimore). 2022 Aug 19;101(33):e27915. doi: 10.1097/MD.0000000000027915.
Finotti M, Romano M, Brizzolari M, Scopelliti M, Zanus G. Comment on: “A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis”. Hepatobiliary Surg Nutr. 2022 Aug;11(4):640-642. doi: 10.21037/hbsn-22-202.
Ozen M, Raissi D. Editorial comment: a review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis. Hepatobiliary Surg Nutr. 2022 Jun;11(3):453-456. doi: 10.21037/hbsn-22-138.
Zhang JY, Chen L, Ma R, Miao CM, Wang YB. Effectiveness and safety of focused ultrasound ablation surgery compared with radiofrequency ablation in primary hepatocellular carcinoma treatment: a meta-analysis. Transl Cancer Res. 2021 May;10(5):2080-2090. doi: 10.21037/tcr-20-3458.
Tsang SH, Ma KW, She WH, Chu F, Lau V, Lam SW, Cheung TT, Lo CM. High-intensity focused ultrasound ablation of liver tumors in difficult locations. Int J Hyperthermia. 2021 Sep;38(2):56-64. doi: 10.1080/02656736.2021.1933217.
Merrill R, Odéen H, Dillon C, Bitton R, Ghanouni P, Payne A. Design and evaluation of an open-source, conformable skin-cooling system for body magnetic resonance guided focused ultrasound treatments. Int J Hyperthermia. 2021;38(1):679-690. doi: 10.1080/02656736.2021.1914872.
Barrere V, Sanchez M, Cambronero S, Dupré A, Rivoire M, Melodelima D. Evaluation of Ultrasonic Attenuation in Primary and Secondary Human Liver Tumors and Its Potential Effect on High-Intensity Focused Ultrasound Treatment. Ultrasound Med Biol. 2021 Apr 21:S0301-5629(21)00135-6. doi: 10.1016/j.ultrasmedbio.2021.03.014.
Hendricks A, Weber P, Simon A, Saunier S, Coutermarsh-Ott S, Grider D, Jove JV, Allen IC, Luyimbazi D, Vlaisavljevich E. Histotripsy for the Treatment of Cholangiocarcinoma Liver Tumors: In Vivo Feasibility and Ex Vivo Dosimetry Study. IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Apr 15;PP. doi: 10.1109/TUFFC.2021.3073563.
Gu L, Shen Z, Ji L, Ng DM, Du N, He N, Fan X, Yan K, Zheng Z, Chen B, Ma L, Qiu G, Chen P, Zheng J, Yang T. High-intensity focused ultrasound alone or combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with unsuitable indications for hepatectomy and radiofrequency ablation: a phase II clinical trial. Surg Endosc. 2021 Mar 31. doi: 10.1007/s00464-021-08465-3.
Click here for additional references from PubMed.
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